Adjuvant arthritis in the rat can be induced by a single injection of an emulsion of certain dried heat killed microorganisms such as Mycobacteria, Corynebacteria, streptococci, or their cell wall components in a suitable oily vehicle. The disease resembles HLA-B27 positive spondylo-arthropathies such as the Reiter's syndrome and shares many similarities with rheumatoid arthritis. The disease has been believed to arise from a cell-mediated immune response to antigen(s) whose identity remains elusive. Results obtained from our recent studies indicated that the etiologic immunogen(s) is derived from the host rather than that from the injected substances. We have found further that autoimmunity to type II collagen is not a major factor in the induction or maintenance of this disease. These findings, together with other considerations, have led us to the belief that the immunogens responsible for the pathogenesis of adjuvant arthritis in the rat are altered self substances formed in the mycobacteria-induced granuloma and resulting from partial degradation by proteolytic enzymes. With the long term goal of elucidating the pathogenesis of this experimental disease, it is the objective of this proposed investigation to test the above hypothesis through three independent approaches: 1) by determining whether a chronic arthritis can be induced in rats under certain immunostimulatory conditions by substances contained in experimental granuloma and 2) by determining whether "tolerance" (with respect to arthritis induction) to Freund's complete adjuvant can be induced by pretreating young rats with oil emulsions of granuloma extract and 3) by determining whether aqueous extracts of inflammed tissue and/or its isolated constituents, e.g. proteoglycans and link proteins, can induce antigen specific blast transformation of lymphocytes from rats with adjuvant arthritis. The proposed study on adjuvant arthritis may lead to a better understanding of the aetiopathogenesis of human rheumatologic diseases which it resembles. Each new advance in our knowledge on the nature and pathogenesis of these diseases represent a new possibility of enlarging our diagnostic and therapeutic spectrum which may lead to a better clinical management.